ORCID Profile
0000-0002-9976-9922
Current Organisation
KU Leuven
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Publisher: Springer Science and Business Media LLC
Date: 23-01-2018
Publisher: Informa UK Limited
Date: 02-09-2014
Publisher: Springer Science and Business Media LLC
Date: 21-07-2023
DOI: 10.1038/S41467-023-39996-Z
Abstract: Obesity is associated with an increased risk of developing breast cancer (BC) and worse prognosis in BC patients, yet its impact on BC biology remains understudied in humans. This study investigates how the biology of untreated primary BC differs according to patients’ body mass index (BMI) using data from ,000 patients. We identify several genomic alterations that are differentially prevalent in overweight or obese patients compared to lean patients. We report evidence supporting an ageing accelerating effect of obesity at the genetic level. We show that BMI-associated differences in bulk transcriptomic profile are subtle, while single cell profiling allows detection of more pronounced changes in different cell compartments. These analyses further reveal an elevated and unresolved inflammation of the BC tumor microenvironment associated with obesity, with distinct characteristics contingent on the estrogen receptor status. Collectively, our analyses imply that obesity is associated with an inflammaging-like phenotype. We conclude that patient adiposity may play a significant role in the heterogeneity of BC and should be considered for BC treatment tailoring.
Publisher: Informa UK Limited
Date: 02-01-2016
Publisher: Research Square Platform LLC
Date: 03-02-2023
DOI: 10.21203/RS.3.RS-2377863/V1
Abstract: Worldwide, there is a growing proportion of women who are overweight or obese. While obesity has been associated with an increased risk of developing breast cancer (BC) and worse prognosis in BC patients, yet the impact of adiposity (abnormal or excess body fat) on BC biology remains understudied in humans. This retrospective study aimed to investigate how the biology of primary BC would differ according to patients’ body mass index (BMI). We examined clinicopathological data (including BMI at the time of diagnosis) and molecular data (including genomic, bulk and single-cell transcriptomic data) of treatment-naïve (early stage) BC patients from five cohorts (N = 2071). We identified several genomic alterations considered actionable or of potential clinical relevance which had a different prevalence in overweight or obese patients compared to lean patients, for instances, less PIK3CA gene mutations, and more CCND1, CCNE1 and IGFR1 lifications. Moreover, we found evidence supporting an ageing accelerating effect of obesity at the genetic level, through its association with an age-associated mutational signature. We showed that BMI-associated differences in transcriptomic profile were subtle at the bulk resolution while single cell profiling allowed detection of more pronounced changes in different cell compartments. Investigation at the single cell resolution revealed an elevated and unresolved inflammation of the BC tumor microenvironment (TME) associated with obesity, which had distinct characteristics contingent on the estrogen receptor status. Collectively, analyses at both genomic and transcriptomic levels implied that obesity is associated with an inflammaging-like phenotype of the TME. Our results indicate that patient adiposity might play a significant role in the heterogeneity of BC and should be considered in the context of precision medicine.
Publisher: Frontiers Media SA
Date: 20-11-2015
Publisher: Springer Science and Business Media LLC
Date: 28-02-2017
DOI: 10.1038/NMETH.4185
Abstract: We argue that the field of extracellular vesicle (EV) biology needs more transparent reporting to facilitate interpretation and replication of experiments. To achieve this, we describe EV-TRACK, a crowdsourcing knowledgebase (evtrack.org) that centralizes EV biology and methodology with the goal of stimulating authors, reviewers, editors and funders to put experimental guidelines into practice.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Abhishek Garg.